title: Hypoxia-induced downregulation of miR-30c promotes epithelial-mesenchymal transition in human renal cell carcinoma.
abstract: MicroRNAs (miRNAs), which negatively regulate protein expression by binding protein-coding mRNAs, have been integrated into cancer development and progression as either oncogenes or tumor suppressor genes. miR-30c was reported to be downregulated in several types of cancer. However, its role in human renal cell carcinoma (RCC) remains largely unknown. Here, we show that miR-30c is significantly downregulated in human RCC tissues and cell lines. We found that miR-30c downregulation could be induced by hypoxia in RCC cells in a hypoxia-inducible factors (HIFs) dependent manner. Repression of miR-30c through its inhibitor resulted in reduction of E-cadherin production and promotion of epithelial-mesenchymal transition (EMT), while overexpression of miR-30c inhibited EMT in RCC cells. We identified Slug as a direct target of miR-30c in RCC cells. Slug was upregulated in RCC tissues and its expression could be induced by hypoxia, which is consistent with downregulation of miR-30c by hypoxia. Forced overexpression of Slug in 786-O cells reduced E-cadherin production, and promoted EMT as well as cell migration. Moreover, Slug overexpression abrogated the inhibitory role of miR-30c in regulating EMT and cell migration, indicating miR-30c regulates EMT through Slug in RCC cells. Our findings propose a model that hypoxia induces EMT in RCC cells through downregulation of miR-30c, which leads to subsequent increase of Slug expression and repression of E-cadherin production, and suggest a potential application of miR-30c in RCC treatment.
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Huang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yao
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Baijun
authors.initials: B
authors.lastname: Dong
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.forename: Dongming
authors.initials: D
authors.lastname: Liu
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C546086:MIRN30b microRNA, human; C000604407:SNAI1 protein, human; C497446:VHL protein, human